title: Structural and functional studies of a 50 kDa antigenic protein from Salmonella enterica serovar Typhi.
abstract: The high typhoid incidence rate in developing and under-developed countries emphasizes the need for a rapid, affordable and accessible diagnostic test for effective therapy and disease management. TYPHIDOT®, a rapid dot enzyme immunoassay test for typhoid, was developed from the discovery of a ∼50 kDa protein specific for Salmonella enterica serovar Typhi. However, the structure of this antigen remains unknown till today. Studies on the structure of this antigen are important to elucidate its function, which will in turn increase the efficiency of the development and improvement of the typhoid detection test. This paper described the predictive structure and function of the antigenically specific protein. The homology modeling approach was employed to construct the three-dimensional structure of the antigen. The built structure possesses the features of TolC-like outer membrane protein. Molecular docking simulation was also performed to further probe the functionality of the antigen. Docking results showed that hexamminecobalt, Co(NH(3))(6)(3+), as an inhibitor of TolC protein, formed favorable hydrogen bonds with D368 and D371 of the antigen. The single point (D368A, D371A) and double point (D368A and D371A) mutations of the antigen showed a decrease (single point mutation) and loss (double point mutations) of binding affinity towards hexamminecobalt. The architecture features of the built model and the docking simulation reinforced and supported that this antigen is indeed the variant of outer membrane protein, TolC. As channel proteins are important for the virulence and survival of bacteria, therefore this ∼50 kDa channel protein is a good specific target for typhoid detection test.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Malaysia. yeesiew@usm.my
authors.forename: Yee Siew
authors.initials: YS
authors.lastname: Choong
authors.forename: Theam Soon
authors.initials: TS
authors.lastname: Lim
authors.forename: Ai Lan
authors.initials: AL
authors.lastname: Chew
authors.forename: Ismail
authors.initials: I
authors.lastname: Aziah
authors.forename: Asma
authors.initials: A
authors.lastname: Ismail
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism; D003035:Cobalt / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D019779:Salmonella enterica / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002712:Chlorides; D008565:Membrane Proteins; C007936:hexaminecobalt (III) trichloride; D003035:Cobalt